2023 World Conference on Lung Cancer (Posters)-P1.22. Predictive Biomarkers of Response to REGN5093 to Guide Patient Selection in MET-Altered Advanced Non-small Cell Lung Cancer

P1.22. Predictive Biomarkers of Response to REGN5093 to Guide Patient Selection in MET-Altered Advanced Non-small Cell Lung Cancer - PDF(Abstract)

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This abstract presents the findings of a study on predictive biomarkers of response to REGN5093, a human bispecific MET antibody, in advanced non-small cell lung cancer (NSCLC). The study aimed to identify biomarkers associated with tumor response and drug resistance to help guide patient selection for REGN5093 therapy. <br /><br />The study included patients with MET-altered NSCLC who received REGN5093 intravenously every three weeks. The biomarkers analyzed included MET exon 14 skipping, gene amplification, genomic profiling, MET protein expression, total soluble MET (sMET), and hepatocyte growth factor (HGF). Response to therapy was evaluated based on overall response rate (ORR) and tumor regression assessed by RECIST criteria.<br /><br />The results showed that the ORR was 13%, and among patients with centrally confirmed MET alterations, the ORR was 27% in patients with MET exon 14 mutations and 36% in patients with MET amplification. Patients with confirmed MET alterations also had known genomic mutations at baseline that could affect the anti-tumor effects of MET inhibition.<br /><br />Early changes in circulating tumor DNA (ctDNA), including the disappearance of MET amplification, were observed post-therapy and correlated with tumor regression in one patient with a durable response. However, changes in total sMET concentrations in serum did not predict therapeutic response.<br /><br />The study highlights the potential of biomarkers to identify patients who are likely to respond to REGN5093 therapy and who may benefit from combination therapies. These findings provide valuable insights for future combination studies of REGN5093 with other therapies in the treatment of NSCLC.<br /><br />In conclusion, the study identifies predictive biomarkers of response and resistance to REGN5093 in MET-altered advanced NSCLC. These biomarkers can aid in patient selection for REGN5093 therapy and inform the design of future combination studies to improve outcomes in NSCLC patients.

Asset Subtitle

Mary Laughlin

Meta Tag

Speaker Mary Laughlin

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

predictive biomarkers

REGN5093

advanced NSCLC

tumor response

MET alterations

MET exon 14 mutations

MET amplification

genomic mutations

circulating tumor DNA

combination therapies